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THROMBOMODULIN DEFICIENCY IN HUMAN DIABETIC NERVE MICROVASCULATURE
Author(s) -
Hafer Macko CE,
Ivey FM,
Gyure KA,
Sorkin JD,
Macko RF
Publication year - 2002
Publication title -
journal of the peripheral nervous system
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 67
eISSN - 1529-8027
pISSN - 1085-9489
DOI - 10.1046/j.1529-8027.2002.02032_9.x
Subject(s) - medicine , pathogenesis , perineurium , von willebrand factor , sural nerve , diabetic neuropathy , microcirculation , ischemia , peripheral neuropathy , pathology , epineurium , diabetes mellitus , endocrinology , platelet , anatomy , peripheral nerve , sciatic nerve
Human diabetic neuropathy is multifactorial in etiology, with ischemia as a final common pathology. Although impaired vascular endothelial cell function in diabetic microvascular injury is established, the role of thrombomodulin (TM)‐dependent protein C antithrombotic mechanism in the pathogenesis of neuropathy is unclear. This neuropathologic case‐control study investigated whether vascular endothelial TM expression is deficient in peripheral nerve microvessels in diabetic neuropathy. Sural nerve biopsies from 7 patients with diabetic neuropathy and 10 with axonal neuropathy without vasculopathy were immunostained with anti‐TM and anti‐von Willebrand factor (vWF; an endothelial cell marker) antibodies. The proportion of TM‐positive microvessels was expressed relative to total vWF‐staining vessels, according to vessel caliber and regional distribution within the nerve. In diabetic nerves compared with reference controls, the proportion of TM‐positive endoneurial microvessels was 15‐fold lower (0.02 vs. 0.30 in diabetic nerves vs. controls, P < 0.004), and the proportion of small‐caliber epineurial microvessels was 10‐fold lower (0.04 vs. 0.43, P < 0.001). No TM expression was detected at the perineurium in diabetic or control nerves. We demonstrate a substantial reduction of vascular endothelial TM expression throughout human diabetic neuropathy. These findings suggest that an impaired native TM‐dependent protein C antithrombotic mechanism may contribute to microvascular ischemia in the pathogenesis of diabetic neuropathy.